| Autor: |
Lee, Dong-Eun, Na, Jin Hee, Lee, Sangmin, Kang, Choong Mo, Kim, Hun Nyun, Han, Seung Jin, Kim, Hyunjoon, Choe, Yearn Seong, Jung, Kyung-Ho, Lee, Kyo Chul, Choi, Kuiwon, Kwon, Ick Chan, Jeong, Seo Young, Lee, Kyung-Han, Kim, Kwangmeyung |
| Zdroj: |
Molecular Pharmaceutics; June 2013, Vol. 10 Issue: 6 p2190-2198, 9p |
| Abstrakt: |
An efficient and straightforward method for radiolabeling nanoparticles is urgently needed to understand the in vivobiodistribution of nanoparticles. Herein, we investigated a facile and highly efficient strategy to prepare radiolabeled glycol chitosan nanoparticles with 64Cu via a strain-promoted azide–alkyne cycloaddition strategy, which is often referred to as click chemistry. First, the azide (N3) group, which allows for the preparation of radiolabeled nanoparticles by copper-free click chemistry, was incorporated to glycol chitosan nanoparticles (CNPs). Second, the strained cyclooctyne derivative, dibenzyl cyclooctyne (DBCO) conjugated with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator, was synthesized for preparing the preradiolabeled alkyne complex with 64Cu radionuclide. Following incubation with the 64Cu-radiolabeled DBCO complex (DBCO-PEG4-Lys-DOTA-64Cu with high specific activity, 18.5 GBq/μmol), the azide-functionalized CNPs were radiolabeled successfully with 64Cu, with a high radiolabeling efficiency and a high radiolabeling yield (>98%). Importantly, the radiolabeling of CNPs by copper-free click chemistry was accomplished within 30 min, with great efficiency in aqueous conditions. In addition, we found that the 64Cu-radiolabeled CNPs (64Cu-CNPs) did not show any significant effect on the physicochemical properties, such as size, zeta potential, or spherical morphology. After 64Cu-CNPs were intravenously administered to tumor-bearing mice, the real-time, in vivobiodistribution and tumor-targeting ability of 64Cu-CNPs were quantitatively evaluated by microPET images of tumor-bearing mice. These results demonstrate the benefit of copper-free click chemistry as a facile, preradiolabeling approach to conveniently radiolabel nanoparticles for evaluating the real-time in vivobiodistribution of nanoparticles. |
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